EQU-001 as an Add-On Drug for People with Focal Seizures while on Medicatio

Phase 1

• Conditions: Epilepsy; MedDRA version: 21.1Level: LLTClassification code: 10016843Term: Focal seizures Class: 10029205; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: CTIS2022-500302-18-00
• Lead Sponsor: Equilibre Biopharmaceuticals B.V.

Brief Summary

Post Results Justification 2022-500302-18

Detailed Description

Not available

Study Timeline

• Study Start: 2022-07-06
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 263

Inclusion Criteria

1. Age 18- 65 years at time of informed consent., 7. Seizures uncontrolled after an adequate trial of at least 1 ASM within the last 2 years., 8. Currently receiving treatment with 1-3 ASMs with doses stable for at least 4 weeks prior to screening. These medications must stay stable during the 8-week baseline period and during the 16-week treatment period. In the case that the plasma level of a concomitant ASM changes, the subject and their physician may then modify the dose to maintain the plasma level that was present prior to beginning the study drug. and must document the change in the EDC system., 9. If participant has a vagal nerve stimulator (VNS), responsive neurostimulator (RNS) or deep brain stimulator (DBS), it must have been implanted and activated >1 year prior to screening, and stimulation parameters that have been stable for >3 months, and battery life of unit anticipated to extend for duration of trial., 10. Females of childbearing potential who are not sexually inactive (abstinent) for 30 days prior to the first dose, throughout the study, and then for 30 days following the last dose, must agree to use of one of the following acceptable birth control methods from 30 days prior to the first dose through 30 days after the last dose of study drug: i. Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) together with a condom or other barrier method ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) together with a condom or other barrier method iii. Intrauterine device (IUD) together with a condom or other barrier method iv. Intrauterine hormone releasing system (IUS) together with a condom or other barrier method v. Bilateral tubal occlusion, hysterectomy, bilateral oophorectomy vi. Vasectomized partner (vasectomy >6 months ago) ? For this study, pre-menopausal is defined as not meeting the clinical criteria for postmenopausal, that is, no menstrual period for at least one year, in the absence of other identifiable cause(s) of not having a period, together with the absence of typical symptoms of menopause, such as hot flashes and mood instability. ? True abstinence is allowable when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception., 2. The subject or designee is willing and able to keep an accurate study diary, the subject is able to adhere to the protocol, the subject or the subject’s legal representative is able read, understand, and sign informed consent, as applicable., 3. Diagnosed with focal epilepsy according to ILAE (2017) criteria. Diagnosis to include clinical history and an EEG consistent with focal epilepsy. A normal interictal EEG is allowed when the clinical history is consistent with focal epilepsy., 4. Subject has no seizures that are not focal by the ILAE 2017 criteria., 5. Subject must have 8 countable, observable focal seizures during the 8-week baseline period prior to randomization, including at least 3 in each 4-week period with no 21-day seizure-free period. These seizures must be observable (focal aware with motor component, focal impaired awareness, focal to bilateral tonic-clonic) and as such may not include focal aware seizures without a detectable motor component, aphasia, or other o

Exclusion Criteria

1. Pregnant or lactating, 7. Presence of progressive neurological disorder or other progressive disorder or unstable medical condition(s) that may confound study results. History of long QT syndrome, family history of sudden death of unknown cause., 8. Psychiatric disorder where changes in pharmacotherapy are needed or anticipated during the study or which would interfere with the subject’s ability to participate in the trial, 10. History of substance use disorder, including alcohol, within the past 2 years, 9. Active suicidal plan/intent in the past 6 months, a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt as evidenced by a positive response to C-SSRS questions 4 or 5, 11. Currently in another investigational drug study, 12. Currently on felbamate for less than one year before visit 1 (aplastic anemia and hepatic failure usually occur within 6 months to one year). If on felbamate, documentation of stable hemogram and liver enzyme tests must be present, 13. Currently on vigabatrin for less than 2 years before visit 1, as most visual field changes occur between 6 months and 2 years Subjects on vigabatrin should have available, appropriate documentation of visual fields, 14. Currently taking retigabine/ezogabine, 15. History of intermittent use of rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period is considered a 1-time rescue) more than once in the 4 weeks prior to the baseline visit or more than once per 4 weeks during the 8-week baseline period. If a subject is taking benzodiazepines for an indication other than epilepsy (e.g., anxiety, sleep), the dose should be stable for at least 4 weeks prior to screening and remain stable throughout screening and double blind periods of the study., 16. Currently taking ivermectin, or has taken it within the last 4 weeks prior to visit 1, 18. Has any of the following laboratory or exam abnormalities: i. Positive urine drug screen (methamphetamines, amphetamines, cocaine, PCP, opioids, barbiturates) at screening without a therapy related explanation ii. Positive hCG (female participants) (at screening or visit 2/enrollment) iii. QTcF > 450 msec at visit 2/enrollment iv. Serum albumin of 25 g/L or less at screening or visit 2/enrollment v. CTP score of 10 or greater at visit 2/enrollment, 17a. Use of the following medications within 4 weeks of the baseline visit and throughout the study that may interfere with study drug metabolism (please note ASMs with CYP3A4 metabolism are not excluded from this study, as drug levels and safety are monitored throughout the study): i. CYP3A4 inducers: rifampin, lumacaftor, mitotane, enzalutamide, apalutamide, St. John’s wort, glucocorticoids (except if given as a rescue anti-seizure medication) ii. Medications with PGP interactions: amiodarone, apalutamide, verapamil, lorlatinib, rifampin, St. John’s wort, elacridar, valspodar, zosuquidar 17b. Use of the following medications/foods is not strictly prohibited but is discouraged. Please make every attempt to refrain and to record each incidence of use of any of these (along with all medications and supplements). ii. CYP3A4 inhibitors, including, but not limited to clarithromycin, ceritinib, idelalisib, lonafarnib, tucatinib, erythromycin, telithromycin, diltiazem, dronedarone, posaconazole, voriconazole, nefazodone, itraconazole, ketoconazole, anti-retroviral drugs (atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir),

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of EQU-001 in doses of 20 mg and 60 mg per day as adjunctive therapy compared with placebo for focal onset seizures in subjects with epilepsy;Secondary Objective: 1. To assess the efficacy of EQU-001 at doses of 20 mg and 60 mg during a maintenance phase, 2. To assess the efficacy of EQU-001 at doses of 20 mg and 60 mg in specified seizure types, 3. To assess the subject’s impression of change at doses of 20 mg and 60 mg, 4. To assess the effect on quality of life of EQU-001 in subjects with focal onset seizures at doses of 20 mg and 60 mg daily, 5. To assess the safety and tolerability of EQU-001 in doses of 20 mg and 60 mg per day in subjects with focal onset seizures;Primary end point(s): Median percentage change in the overall number of countable observable seizures per 28 day period relative to baseline in each treatment arm during the double-blind treatment period compared with placebo